Hirai et al. BMC Infectious Diseases (2020) 20:821 https://doi.org/10.1186/s12879-020-05564-9

RESEARCH ARTICLE Open Access Clinical characteristics of community- acquired due to in adults: a retrospective single- centre study Jun Hirai1,2, Takeshi Kinjo2* , Tomomi Koga1,3, Shusaku Haranaga2, Eiji Motonaga4 and Jiro Fujita2

Abstract Background: Although Moraxella catarrhalis (M. catarrhalis) is a common cause of community-acquired pneumonia (CAP), studies investigating clinical manifestations of CAP due to M. catarrhalis (MC-CAP) in adults are limited. Since S. pneumoniae is the leading cause of CAP globally, it is important to distinguish between MC-CAP and CAP due to S. pneumoniae (SP-CAP) in clinical practice. However, no past study compared clinical characteristics of MC-CAP and SP-CAP by statistical analysis. We aimed to clarify the clinical characteristics of MC-CAP by comparing those of SP- CAP, as well as the utility of sputum Gram staining. Methods: This retrospective study screened CAP patients aged over 20 years visiting or admitted to Okinawa Miyako Hospital between May 2013 and April 2018. Among these, we included patients whom either M. catarrhalis alone or S. pneumoniae alone was isolated from their sputum by bacterial cultures. Results: We identified 134 MC-CAP and 130 SP-CAP patients. Although seasonality was not observed in SP-CAP, almost half of MC-CAP patients were admitted in the winter. Compared to those with SP-CAP, MC-CAP patients were older (p < 0.01) and more likely to have underlying pulmonary diseases such as asthma and bronchiectasis (p < 0.01). Approximately half of asthmatic MC-CAP and SP-CAP patients had asthma attacks. Although winter is an influenza season in Japan, co-infection with influenza virus was less common in MC-CAP compared to SP-CAP patients (3% vs. 15%, p < 0.01). Bronchopneumonia patterns on X-ray, as well as bronchial wall thickening, bilateral distribution, and segmental pattern on CT were more common in MC-CAP patients than in SP-CAP patients (p < 0.01). Sputum Gram stain was highly useful method for the diagnosis in both MC-CAP and SP-CAP (78.4% vs. 89.2%), and penicillins were most frequently chosen as an initial treatment for both . (Continued on next page)

* Correspondence: [email protected] 2Department of Infectious, Respiratory and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan Full list of author information is available at the end of the article

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(Continued from previous page) Conclusions: This is the first study to show that MC-CAP occurred in older people compared to SP-CAP, influenza virus co-infection was less common in MC-CAP than SP-CAP, and that MC-CAP frequently caused asthma attacks. Gram stain contributed for the appropriate treatment, resulting in conserving broad-spectrum antibiotics such as cephalosporins and fluoroquinolones in both MC-CAP and SP-CAP patients. Keywords: Moraxella catarrhalis, Streptococcus pneumoniae, Community-acquired pneumonia, Adult, Winter, Asthma, Bronchiectasis, Influenza virus, Bronchopneumonia pattern, Gram stain

Background use of broad-spectrum antibiotics, can inhibit the emer- Although Moraxella catarrhalis is a common bacterial gence of drug-resistant . Therefore, evaluation of cause of community-acquired pneumonia (CAP) [1, 2], the utility of Gram staining is especially important in the detailed information regarding the clinical features of post-antibiotic era. CAP due to M. catarrhalis (MC-CAP) in adults is lim- In the current study, the clinical characteristics of ited. It is generally considered that the incidence of MC- MC-CAP were evaluated by comparison with those of CAP is high in the elderly and persons with chronic pul- SP-CAP. Additionally, diagnostic utility of Gram staining monary diseases in the winter season; however, this in- and choosing antibiotics based on Gram stain result formation is based on descriptive studies, most of which were also evaluated. date back to the 1980s, and the number of patients in- cluded in these studies was relatively small [3–5]. There Methods have been only two studies on MC-CAP published with Patients and study design a sample size of > 100 patients [4, 5]. In addition, previ- In this retrospective observational study, we initially ous studies have not excluded patients co-infected with screened consecutive adult CAP patients aged over 20 other respiratory bacteria, so the clinical features of MC- years, in whom pneumonia had developed during daily M. catarrhalis CAP isolated only by bacterial culture are community living, who visited or were admitted to Oki- unclear [4, 5]. In terms of radiological features of MC- nawa Miyako Hospital (an acute care hospital on Miyako CAP, Okada et al. [6] assessed pulmonary computed Island, Okinawa, Japan) between May 2013 and April M. cat- tomography (CT) findings in patients with acute 2018. We extracted patients that had either M. catarrha- arrhalis pulmonary infection. However, 75 of 109 pa- lis alone or S. pneumoniae alone, as determined by bac- tients (68.8%) had nosocomial infection, and radiological terial culture from their expectorated sputum with findings of MC-CAP were not specifically described. grades P1, P2, or P3 as classified by Miller and Jones M. catarrhalis Additionally, although causes acute ex- [11]. Thus, patients co-infected with other respiratory acerbation of chronic obstructive pulmonary disease bacteria were excluded in this study. (COPD) [7, 8], none of the previous studies have investi- gated the relationship between asthma attacks and MC- Definition of CAP and pneumonia diagnosis CAP. Moreover, while it is well known that antecedent The diagnosis of CAP was based on the presence of clin- influenza virus infection can induce secondary Strepto- ical lower respiratory symptoms such as cough, expecto- coccus pneumoniae pneumonia [9], the association be- rated sputum, and dyspnoea in addition to fever (≥37 °C) tween influenza virus infection and MC-CAP in adults combined with new pulmonary infiltrates on chest X-ray remains unknown. Furthermore, no studies have made [12]. Patients were excluded if they met the following statistical comparisons of the clinical features of MC- conditions: 1) they were under corticosteroids and/or CAP and CAP due to S. pneumoniae (SP-CAP) in adults. other immunosuppressive therapy; 2) antibiotic therapy Because S. pneumoniae is the leading cause of CAP glo- was initiated before collecting sputum and blood for bally, it is useful for physicians to be able to distinguish bacterial culture; 3) presence of other diseases that com- between MC-CAP and SP-CAP in clinical practice. plicate respiration and make it difficult to accurately Gram stain examinations are easy, rapid, and useful diagnose pneumonia, such as acute heart failure; and 4) for identifying causative bacteria; however, it is recently residing in a nursing home or a long-term care facility. abandoned in the US and European countries partially for non-scientific reasons such as legal and economic pressures [10]. In our facility, attending physicians per- Evaluation severity of CAP form Gram staining themselves and choose an initial The CURB-65 score recommended by the British Thor- antibiotic based on the result. Gram stain-guided choice acic Society was used to evaluate the severity of CAP of narrow-spectrum antibiotics, rather than empirical [13], and the Quick Sepsis-related Organ Failure Assess- ment (qSOFA) score was used to screen for sepsis [14]. Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 3 of 9

Data collection Statistical analysis Data were retrospectively collected from medical re- We used Pearson’s χ2 or Fisher’s exact test and the cords. Two sets of blood cultures were obtained from Mann-Whitney U test to compare characteristics of every patient before administrating antimicrobial agents. MC-CAP and SP-CAP patients for categorical and con- Additionally, a rapid influenza diagnostic test was per- tinuous variables, respectively. A p-value of < 0.05 was formed on all patients upon admission. COPD exacerba- considered statistically significant. All data were analysed tion and asthma attack were defined as conditions using R version 2.13.1 (R Foundation for Statistical presenting with shortness of breath, wheezing, and in- Computing, Vienna, Austria). hospital administration of bronchodilator or corticoste- roids. Chest X-ray and CT were evaluated by two physi- Ethical approval cians (one radiologist and one pulmonologist). On chest The Institutional Ethics Committee of Okinawa Miyako X-ray, bronchopneumonia pattern includes multiple Hospital approved this study (approval number 18 areas of small nodular and/or patchy consolidation with- M005). The need for informed consent from each pa- out air bronchogram. While, lobar pneumonia, also tient for inclusion in this study was waived because this known non-segmental pneumonia, pattern shows a soli- study was retrospective, and there were no study-related tary, peripheral focus of dense opacity with air interventions. bronchogram. Results Sputum evaluation, intubation, and antimicrobial Clinical characteristics of MC-CAP and SP-CAP patients susceptibility During the study period, 134 and 130 patients were di- Gram stain of sputum was performed in all patients upon agnosed as MC-CAP and SP-CAP, respectively (Fig. 1). admission. Polymicrobial pattern was defined as the pres- Although seasonality was not observed in SP-CAP, al- ence of many different bacteria without a predominant most half (50.7%) of MC-CAP patients were admitted in bacterium upon Gram stain. The presumptive bacteria winter (Fig. 2). As shown in Fig. 3, both conditions fre- and their morphotypes were as follows: gram-positive, quently occurred in the elderly, with the greatest num- lancet-shaped diplococci for S. pneumoniae, and gram- ber of MC-CAP and SP-CAP patients being in their 80s negative diplococci for M. catarrhalis. Sputum speci- and 70s, respectively. mens were cultured on sheep blood agar and incu- Patients’ backgrounds and clinical characteristics are bated at 37 °C in 5% CO2 for 24–48 h. The shown in Table 1. The mean age of MC-CAP patients was phenotypic identification of isolates and antibiotic significantly higher than that of SP-CAP patients (75.2 vs. susceptibility testing was performed by VITEK 2 66.2 years; p < 0.01). There were no statistically significant (bioMérieux, Marcy-l’Étoile, France). The breakpoint differences in the sex and smoking history between the for susceptibility testing was based on Clinical La- two groups. Body mass index in MC-CAP patients was boratory Standards Institute (CLSI) M100-S22. higher than in SP-CAP patients (23.6 vs. 22.4; p <0.05).

Fig. 1 Flow chart showing the selection for MC-CAP and SP-CAP patients for this study. Eligible patients were further selected by applying the exclusion criteria described in the Materials and Methods section Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 4 of 9

between the two groups. Approximately half of the patients with previously diagnosed asthma in each group experienced asthma attacks. Bacteremic pneu- monia occurred in only 0.7 and 1.5% of MC-CAP and SP-CAP patients, respectively (p = 0.54). All M. catarrhalis isolates produced beta-lactamase, while all S. pneumoniae isolates were susceptible to penicillin. Most MC-CAP and SP-CAP patients were treated with penicillins or cephalosporins, and there were no significant differences in the selection of initial antibiotics other than tetracyclines among the two groups. Nearly two-thirds of patients in both groups were hospitalised, and there was no statistically signifi- cant difference in the duration of antibiotic treatment or the length of hospital stay between the two groups. All Fig. 2 Seasonality of MC-CAP and SP-CAP. Spring: March to May; patients with MC-CAP or SP-CAP received oral and Summer: June to August; Fall: September to November; Winter: December to February intravenous antibiotics targeting susceptible isolates, and there were no deaths in either group.

MC-CAP patients were more likely than those with SP- Radiological findings CAP to have underlying pulmonary diseases such as Chest radiography and CT findings in MC-CAP and SP- asthma (p < 0.01) and bronchiectasis (p < 0.01), and CAP patients are shown in Table 2. The bronchopneu- were more likely to be using home oxygen therapy monia pattern on chest X-ray was similar in both (p < 0.01). In addition, chronic heart failure (p < 0.01) groups. However, this pattern was more frequently ob- and chronic kidney disease (p < 0.01) were more fre- served in MC-CAP patients than in those with SP-CAP quent in MC-CAP patients. A relatively small propor- (p < 0.01). Among the 18 MC-CAP patients and 23 SP- tion of each group had severe pneumonia according CAP patients who had chest CT scans, bronchial wall to their CURB-65 score, and only 3.7% of MC-CAP thickening (66.7 vs. 26.1%; p < 0.01), bilateral distribution and 6.2% of SP-CAP patients had a positive qSOFA (88.9 vs. 47.8%; p < 0.01), and segmental pattern (100 vs. score (≥2). In terms of clinical manifestations and la- 69.5%; p < 0.01) were more common in MC-CAP pa- boratory data, the proportions of high fever (p < 0.01), tients. Of the SP-CAP patients, 30.4% had a pleural effu- systolic blood pressure ≤ 100 mmHg (p < 0.05), shaking sion while none of the MC-CAP patients had a pleural chill (p < 0.01), elevated white blood cell counts (p < effusion (p < 0.01). 0.05), and a positive influenza rapid test (p < 0.01) were significantly higher in patients with SP-CAP Gram stain and initial treatment than in those with MC-CAP. There was no significant The sensitivity of the Gram stain for MC-CAP diagnosis difference in the frequency of COPD exacerbation was significantly lower than that for S. pneumoniae (78.4 vs. 89.2%; p < 0.05). M. catarrhalis was most frequently misidentified as (8.2%) or S. pneumoniae (6%), while S. pneumoniae was most fre- quently misidentified as M. catarrhalis (3.1%) (Table 3).

Discussion As mentioned earlier, current knowledge about the clin- ical features of MC-CAP in adults is based on old stud- ies, and most of these studies are descriptive [1–5]. In the current study, we used statistical inference to com- pare the clinical characteristics of CAP caused by M. catarrhalis infections with those with CAP cause by S. pneumoniae infections. In addition to reconfirming the previously known characteristics of MC-CAP, we found for the first time that co-infection with influenza virus was less common in MC-CAP patients compared to Fig. 3 Age distribution for MC-CAP and SP-CAP patients those with SP-CAP, even though half of MC-CAP Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 5 of 9

Table 1 Baseline characteristics of MC-CAP and SP-CAP patients MC-CAP (%) SP-CAP (%) P valuea Number of patients 134 130 Background Age: mean ± SD 75.2 ± 15.6 66.2 ± 17.4 < 0.01 Gender (M/F) 72/62 64/66 0.46 Body mass indexb, mean ± SD 23.6 ± 5.6 22.4 ± 3.5 < 0.05 Ever smoker 55 (41) 42 (32.3) 0.14 Underlying pulmonary disease Asthma 51 (38.1) 25 (19.2) < 0.01 Bronchiectasis 56 (41.8) 22 (16.9) < 0.01 Chronic obstructive pulmonary disease (COPD) 35 (26.1) 26 (20) 0.24 Interstitial pneumonia 6 (4.5) 1 (0.8) 0.06 Lung cancer 6 (4.5) 4 (3.1) 0.55 Old tuberculosis 15 (11.2) 10 (7.7) 0.33 Under home oxygen therapy 16 (11.9) 4 (3.1) < 0.01 Usage continuous positive airway pressure therapy 6 (4.5) 1 (0.8) 0.06 Systemic underlying disease Cerebrovascular disease 7 (5.2) 4 (3.1) 0.38 Chronic heart failure 41 (30.6) 18 (13.8) < 0.01 Chronic kidney disease 15 (11.2) 3 (2.3) < 0.01 Collagen disease 3 (2.2) 0 (0) 0.08 Diabetes mellitus 23 (17.2) 14 (10.8) 0.13 Hypertension 64 (47.8) 48 (36.9) 0.07 Malignancy 15 (11.2) 8 (6.2) 0.14 Severity CURB-65 Mild 96 (71.6) 103 (79.2) 0.15 Moderate 32 (23.9) 22 (16.9) 0.16 Severe 6 (4.5) 5 (3.8) 0.79 qSOFA ≥ 2 5 (3.7) 8 (6.2) 0.36 Clinical manifestation High fever (≥38 °C) 50 (37.3) 80 (61.5) < 0.01 Systolic blood pressure ≤ 100 mmHg 3 (2.2) 11 (8.5) < 0.05 Shaking chill 8 (6) 26 (20) < 0.01 COPD exacerbation 10/35 (28.6) 5/26 (19.2) 0.4 Asthma attack 24/51 (47) 13/25 (52) 0.68 Laboratory data White blood cellc, mean ± SD 11,451 ± 4556 12,543 ± 5118 < 0.05 C-reactive proteind, mean ± SD 8.2 ± 7.4 9.1 ± 7.6 0.17 Serum albumine, mean ± SD 3.6 ± 0.5 3.7 ± 0.5 0.21 Positive for influenza virus rapid test 4 (3) 19 (14.6) < 0.01 Blood culture Positive 1 (0.7) 2 (1.5) 0.54 Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 6 of 9

Table 1 Baseline characteristics of MC-CAP and SP-CAP patients (Continued) MC-CAP (%) SP-CAP (%) P valuea Initial treatment Penicillin (ABPC, ABPC/SBT, AMPC, or AMPC/CVA) 70 (52.2) 71 (54.6) 0.69 Cephalosporin (CTM, CTRX, CTX, or CMZ) 48 (35.8) 51 (39.2) 0.57 Macrolides (AZM) 8 (6) 6 (4.6) 0.62 Tetracyclines (MINO) 5 (3.7) 0 (0) < 0.05 Fluoroquinolones (LVFX) 2 (1.5) 1 (0.8) 0.57 Outcome Hospitalised patients 79 (59) 76 (58.4) 0.93 Length of antibiotic treatment, mean ± SD 6.8 ± 2.2 7.1 ± 2.3 0.17 Length of hospital stay, mean ± SD 9.2 ± 4.7 8.6 ± 3.0 0.19 In-hospital mortality 0 0 – Abbreviations: COPD chronic obstructive pulmonary disease, SD standard deviation, ABPC ampicillin, ABPC/SBT ampicillin sulbactam, AMPC amoxicillin, AMPC/CVA amoxicillin clavulanate, CTM cefotiam, CTRX ceftriaxone, CTX cefotaxime, CMZ cefmetazole, AZM azithromycin, MINO minocycline, LVFX levofloxacin aStatistical differences between MC-CAP and SP-CAP were evaluated by Pearson’s χ2 or Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables bNumber of patients was 108 in MC-CAP and 93 in SP-CAP cNumber of patients was 118 in MC-CAP and 113 in SP-CAP dNumber of patients was 117 in MC-CAP and 109 in SP-CAP eNumber of patients was 98 in MC-CAP and 91 in SP-CAP

patients were admitted during the influenza season. Fur- thermore, both MC-CAP and SP-CAP frequently caused asthma attacks. Table 2 Chest X-ray and CT findings in MC-CAP and SP-CAP As shown in previous studies [1, 3, 15], MC-CAP pa- patients tients in the present study were frequently admitted in MC-CAP (%) SP-CAP (%) P valuea winter. The reason for this pattern is unknown. Some in- Chest X-ray vestigators have described an association with a preceding or concurrent viral infection [16, 17], but our data show Number of patients 134 130 that influenza virus infection is not common in MC-CAP. Bronchopneumonia pattern 127 (94.8) 84 (64.6) < 0.01 Infections with other respiratory viruses were not exam- Lobar pneumonia pattern 7 (5.2) 46 (35.4) < 0.01 ined in this study; therefore, any associations with other Chest CT respiratory viruses remain undetermined. Borges et al. Number of patients 18 23 [18] showed that the occurrence of MC-CAP in children Findings in tropical regions was positively associated with low hu- midity and negatively associated with air temperature and Consolidation 6 (33.3) 19 (82.6) < 0.01 sunshine, suggesting that climatic conditions might ac- Air bronchogram 3 (16.7) 17 (73.9) < 0.01 count for the seasonality of MC-CAP. Further studies are Ground glass opacities 7 (38.9) 20 (87) < 0.01 needed to address this question. Bronchial wall thickenings 12 (66.7) 6 (26.1) < 0.01 MC-CAP was more common in the elderly and more Centrilobular nodules 12 (66.7) 20 (87) 0.11 likely to complicate underlying pulmonary diseases in Nodules (5–30 mm) 7 (38.9) 17 (73.9) < 0.05 the present study, a result that is consistent with previ- ous studies [19, 20]. Elderly patients’ propensity to de- Pleural effusion 0 (0) 7 (30.4) < 0.01 velop MC-CAP might be explained by the asymptomatic Lymph node enlargement 2 (11.2) 10 (43.5) < 0.05 (over 1 cm diameter) Table 3 Microorganisms assumed by Gram stain Distribution MC-CAP (%) SP-CAP (%) Unilateral 2 (11.1) 12 (52.2) < 0.01 M. catarrhalis 105 (78.4) 4 (3.1) Bilateral 16 (88.9) 11 (47.8) < 0.01 H. influenzae 11 (8.2) 0 Segmental pattern 18 (100) 16 (69.5) < 0.01 S. pneumoniae 8 (6) 116 (89.2) Non-segmental pattern 0 (0) 7 (30.4) < 0.01 Polymicrobial 9 (6.7) 9 (6.9) a Statistical differences between MC-CAP and SP-CAP were evaluated by None 1 (0.7) 1 (0.8) Pearson’s χ2 or Fisher’s exact test Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 7 of 9

carriage rate of M. catarrhalis. The carriage rate in those By having attending physicians perform a Gram stain, under 60 years old (5%) increases to 25% in those over we could treat pneumonia patients with targeted, 60 years old [19]. Past studies have shown that wide- narrow-spectrum antibiotics in this study, rather than spread use of pneumococcal vaccines increases the empirical, broad-spectrum antibiotics such as cephalo- prevalence of M. catarrhalis colonisation in the respira- sporins and quinolones. tory tract [21, 22]. Therefore, we expect to see an in- The mortality rate of MC-CAP patients in this study crease in the incidence of MC-CAP, particularly among was 0% even though previous studies have revealed rates the elderly, as the global population ages and pneumo- ranging from 5 to 21.4% [1, 4, 6, 28]. In fact, most pa- coccal vaccine coverage increases. For this reason, we tients included in this study were not classified as having must pay attention to the epidemiological trends of MC- severe pneumonia according to the CURB-65 score. This CAP in elderly patients. might be because we excluded patients who were bed- To the best of our knowledge, no previous studies ridden, residing in a nursing home, receiving an im- have investigated the rate of asthma attacks in MC-CAP munosuppressive therapy, or had other diseases patients. As M. catarrhalis adheres to mucosal surfaces complicating respiration, such as acute heart failure. We and induces an inflammatory response in bronchial epi- also excluded patients with concurrent bacterial co- thelial cells, it is not surprising that it can trigger an infection; excluding these patients might affect the mor- asthma attack [23, 24]. In addition, Alnahas et al. [25] tality. In addition, Gram stain-guided appropriate selec- demonstrated that M. catarrhalis infection induced IL- tion of antibiotics might reduce mortality. It is 17 and TNF-α production in the airways and triggered noteworthy that zero mortality was achieved with a asthma attacks in murine models. Thus, additional clin- penicillin-centred choice of antibiotics. Since Gram ical studies are needed to clarify the relationship be- staining is generally performed by attending physicians tween asthma attacks and M. catarrhalis infection. for all patients in most hospitals in Okinawa [10], this Studies of the radiological features of MC-CAP are study reconfirms the validity of Gram stain-guided limited. Additionally, no past studies have compared the prompt decision making in clinical practice. radiological findings of MC-CAP and SP-CAP. Okada The present study has several strengths. Firstly, the et al. [6] investigated 109 CT scans conducted on pa- number of MC-CAP patients included in this study was tients with M. catarrhalis pneumonia (only 34 of 109 larger than that in the previous studies. Additionally, we patients had CAP) and found that the most common excluded MC-CAP patients co-infected with other re- radiological findings were ground glass opacities (91%) spiratory bacteria; therefore, our study population was followed by bronchial wall thickening (78%), centrilobu- appropriate for evaluating the characteristics of MC- lar nodules (73%), and consolidation (49%). These find- CAP. Secondly, rather than performing a descriptive ings were similar to our findings, suggesting that these study, we evaluated the characteristics of MC-CAP by findings are characteristic of M. catarrhalis respiratory comparing them with those of SP-CAP. Thirdly, our infection regardless of the pneumonia classification as study is the first to determine the co-infection rate of CAP or hospital-acquired pneumonia. MC-CAP with influenza virus as well as the rate of Gram stain examination is a simple and rapid diagnos- asthma attacks among MC-CAP patients. tic tool for the presumptive identification of causative Our study has certain limitations. Firstly, it was a bacteria in patients with CAP. Its diagnostic usefulness retrospective study conducted in a single centre. Sec- in the selection of appropriate antibiotics in clinical ondly, it is possible that some MC-CAP patients had co- practice has been investigated in several previous studies infection with additional unidentified atypical pathogens [26, 27]. In the current study, the sensitivity of sputum and viruses. However, co-infection with atypical bacteria Gram stain for MC-CAP diagnosis was lower than that and respiratory viruses was not common in MC-CAP for SP-CAP; however, the rate was relatively high. Fuku- [29]; therefore, this limitation may not significantly affect yama et al. [26] reported that the sensitivity of sputum our results. Finally, we did not perform chest CT exami- Gram stain for MC-CAP diagnosis was higher than that nations in all pneumonia patients. However, only one for SP-CAP diagnosis (85.0% vs. 63.1%), although the study in the literature examined the characteristics of number of patients included the study was small (20 and chest CT findings in MC-CAP patients, and our results 76 patients with MC-CAP and SP-CAP, respectively). were similar to the findings of that study [6]. Our data show that Gram stain can guide the appropri- ate use of antibiotics; more than half the MC-CAP and Conclusions SP-CAP patients were treated with penicillins. Drug- We were able to elucidate the clinical features of MC- resistant bacteria are an increasingly serious problem CAP by performing a statistical comparison with SP- worldwide, and we need conserve existing antibiotic CAP. We revealed for the first time that co-infection drugs, particularly broad-spectrum antimicrobial agents. with influenza virus was less common in MC-CAP Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 8 of 9

patients, and that MC-CAP caused asthma attack in Received: 21 January 2020 Accepted: 30 October 2020 similar frequency to SP-CAP. Additionally, we showed that Gram staining contributes to the appropriateness of treatments, resulting in reducing broad-spectrum anti- References 1. Wright PW, Wallace RJ Jr, Shepherd JR. A descriptive study of 42 cases of biotic use and lowering mortality. Physicians should be Branhamella catarrhalis pneumonia. Am J Med. 1990;88:2S–8S. aware of MC-CAP because it will likely increase in 2. Chin NK, Kumarasinghe G, Lim TK. Moraxella catarrhalis respiratory infection prevalence with the proliferation of pneumococcal vac- in adults. Singap Med J. 1993;34:409–11. 3. McLeod DT, Ahmad F, Power JT, Calder MA, Seaton A. Bronchopulmonary cines as the global population ages. infection due to Branhamella catarrhalis. Br Med J (Clin Res Ed). 1983;287: 1446–7. 4. Slevin NJ, Aitken J, Thornley PE. 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Bacterial Ethics approval and consent to participate and viral etiology in hospitalized community acquired pneumonia with There are no ethical problems or conflict of interests with regard to this – manuscript. The medical records of all confirmed cases were retrospectively molecular methods and clinical evaluation. J Infect Dev Ctries. 2014;8:510 8. reviewed, with identifying information removed. The study was reviewed 17. Johansson N, Kalin M, Hedlund J. Clinical impact of combined viral and bacterial infection in patients with community-acquired pneumonia. Scand and approved by the Institutional Ethics Committee of Okinawa Miyako – Hospital approved this study (approval number 18 M005). J Infect Dis. 2011;43:609 15. 18. Borges IC, Andrade DC, Cardoso MA, Meinke A, Barral A, Käyhty H, et al. Seasonal patterns and association of meteorological factors with infection Consent for publication caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella Not applicable. The medical records of all confirmed cases were catarrhalis in childhood community-acquired pneumonia in a tropical retrospectively reviewed, with identifying information removed. region. Infect Dis (Lond). 2017;49:147–50. 19. Vaneechoutte M, Verschraegen G, Claeys G, Weise B, Van den Abeele AM. Respiratory tract carrier rates of Moraxella (Branhamella) catarrhalis in adults Competing interests and children and interpretation of the isolation of M. catarrhalis from The authors declare that they have no competing interests. sputum. J Clin Microbiol. 1990;28:2674–80. 20. Maruyama T, Gabazza EC, Morser J, Takagi T, D'Alessandro-Gabazza C, Author details Hirohata S, et al. Community-acquired pneumonia and nursing home- 1Department of Internal Medicine, Okinawa Miyako Hospital, Okinawa, Japan. acquired pneumonia in the very elderly patients. Respir Med. 2010;104:584– 2Department of Infectious, Respiratory and Digestive Medicine, Graduate 92. School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, 21. Oikawa J, Ishiwada N, Takahashi Y, Hishiki H, Nagasawa K, Takahashi S, et al. Okinawa 903-0215, Japan. 3Department of Radiology, Graduate School of Changes in nasopharyngeal carriage of Streptococcus pneumoniae, Medicine, University of the Ryukyus, Okinawa, Japan. 4Department of General Haemophilus influenzae and Moraxella catarrhalis among healthy children Medicine, Okinawa Miyako Hospital, Okinawa, Japan. attending a day-care Centre before and after official financial support for Hirai et al. BMC Infectious Diseases (2020) 20:821 Page 9 of 9

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